直接のタンパク質S-パーソルフィデーションへ:直接に水素パーソルフィードを供給するプロドラッグアプローチ
Bingchen Yu1, Yueqin Zheng1, Zhengnan Yuan1
1Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University , Atlanta, Georgia 30303, United States.
Journal of the American Chemical Society
|December 7, 2017
まとめ
研究者は硫黄シグナリングの研究のために新しい硫黄水素 (H2S2) プロドラッグを開発しました. これらの前薬は,S- 超硫化がグリセラルデヒド3- リン酸脱水素酶の活性を低下させることを確認した.
科学分野:
- 生化学と化学生物学
- 酵素運動
- 硫黄の信号伝達経路
背景:
- 硫化水素 (H2S2) は重要な信号分子である.
- 生物学的研究のためにH2S2を直接提供することは困難です.
- タンパク質S-パーセルフィデーションは,重要な翻訳後の改変である.
研究 の 目的:
- 硫化水素 (H2S2) を供給する一般的な戦略を策定する.
- エステラゼとフォスファタゼに敏感なH2S2前薬の合成と検証
- 酵素活性におけるS-パーセルフィデーションの役割を調査する.
主な方法:
- 新しいH2S2プロドラッグの合成 調節可能な放出運動学
- グリセラルデヒド3リン酸脱水酵素の活性を測定する酵素アッセイ
- タンパク質のS-パーセルフィデーションを検証するインビトロ試験
主要な成果:
- エステラゼとフォスファタゼに敏感な H2S2 前薬の合成に成功した.
- タンパク質S- パーソルフィデーションの研究におけるこれらの前薬の有用性を実証した.
- S-パースルフィデーションはグリセラルデヒド3リン酸脱水酵素の活性を低下させることが再確認された.
結論:
- H2S2を直接供給するための新しい戦略が確立されています.
- 合成された前薬は硫黄シグナル研究に貴重なツールを提供します.
- このアプローチは,硫黄種を供給する既存の方法を補完します.
関連する概念動画
Preparation and Reactions of Thiols
7.6K
Thiols are prepared using the hydrosulfide anion as a nucleophile in a nucleophilic substitution reaction with alkyl halides. For instance, bromobutane reacts with sodium hydrosulfide to give butanethiol.
7.6K
Preparation and Reactions of Sulfides
5.9K
Sulfides are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohol. Like ethers, sulfides also consist of two hydrocarbon groups bonded to the central sulfur atom. Depending upon the type of groups present, sulfides can be symmetrical or asymmetrical. Symmetrical sulfides can be prepared via an SN2 reaction between 2 equivalents of an alkyl halide and one equivalent of sodium sulfide.
5.9K
Phase II Reactions: Sulfation and Conjugation with α-Amino Acids
1.1K
Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme...
1.1K
Drug Metabolism: Phase II Reactions
5.3K
Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
5.3K
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
3.9K
Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
3.9K
Sulfur Assimilation
389
Sulfur is an essential element in biological systems, contributing to synthesizing key biomolecules, including amino acids such as cysteine and methionine, and cofactors such as coenzyme A and biotin. Microorganisms primarily assimilate sulfur as sulfate (SO₄²⁻) from the environment, which must undergo a series of biochemical transformations before it can be incorporated into cellular components. As sulfate is highly oxidized, it must undergo assimilatory sulfate reduction to...
389


